An attempt will be made in both an experimental animal model as well as in clinical studies to demonstrate that 5-fluorouracil is formed following oral administration of 5-fluorocytosine. The levels of 5-fluorouracil formed may be significant enough to account for the observed clinical toxicity with 5-fluorocytosine. An attempt will be made to determine the site of conversion of 5-fluorocytosine to 5-fluorouracil, with particular attention being directed to the possible role of intestinal microflora. Following successful development of an animal model, attempts will be made to devise methods of preventing toxicity, which then may be extended to the clinical setting. An ultimate goal of this study is the development of a better pharmacokinetic understanding of 5-FU, with determination of the critical drug level and duration of exposure to 5-FU required to cause toxicity. An improved understanding of these factors may be of additional potential therapeutic benefit in defining toxicity arising from 5-FU administrated in different drug forms (such as Ftorafur, Bia-Ftorafur, or 5 -deoxy-Fluorouridine), as well as accounting for the differential toxicity observed when 5FU is administered at varying rates of infusion.